The Role of the Androgen Receptor in Erythropoiesis*

5α - and 5β-dihydrotestosterone (DHT) were used to evaluate the role of the androgen receptor in stimulating erythropoieais in normal and androgen-insensitive Tfm/Y mice, which lack effective androgen receptors. Mice were made polycythemic before the start of treatment to decrease endogenous erythropoietin production. Incorporation of 59Fe into red blood cells was used to evaluate the overall erythropoietic response. In normal polycythemic mice, 5α-DHT stimulated maximal 59Fe incorporation at a dose of 2.5 mg/day. 5β-DHT induced a smaller response that was maximal at a lower dose (0.125 mg/day). Similar results were achieved with normocythemic mice. The response of Tfm/Y mice to both 5α - and 5β-DHT was similar to that of normal female littermates. A 10-fold excess dose of the nonsteroidal antiandrogen flutamide had no endogenous effect on 59Fe incorporation but did inhibit the increase in iron incorporation induced by both α - and 5β-DHT. In contrast, a 10-fold excess dose of the antiandrogen cyproterone acetate was ineffective in blocking the erythropoietic response stimulated by these steroids. To evaluate the response of the pluripotential bone marrow stem cell to in vitro steroid treatment, the number of spleen colony-forming units (CFU-S) after the incorporation of lethal doses of 3H-thymidine during DNA synthesis were monitored. 5α -DHT had minimal effects but 5β-DHT produced a marked proliferation of the pluripotential cells in normal as well as Tfm/Y mice. Flutamide inhibited the response to 5β-DHT in a dose-response fashion. These data, especially the response of the Tfm/Y mouse, suggest that the androgen receptor may not be essential for the effects of androgens or 5β- steroids on erythropoiesis.